The advent of simple and rapid synthetic procedures for the synthesis of oligodeoxynucleotides from protected deoxynucleotides has resulted in a substantial number of physical and biological investigations of mismatch base pairs (Aboul-ela, et al, Nucleic Acid Research, 14:4811, 1985) and investigations of base pairs where one base is an analog (Jiricny, et al., Nucleic Acid Research, 14:6579, 1986).
The question of whether it is possible to design a pair of bases that could function as an additional complementary base pair in the genetic apparatus of cells has not been explored. The criteria used to design complementary base pairs should address the issues of stability, biochemical pathways for the synthesis of (deoxy)nucleoside triphosphates from bases and/or nucleosides, analog inhibition of essential metabolic pathways, DNA and RNA polymerase utilization of the (deoxy)nucleoside triphosphates, DNA polymerase error frequency and error correction, and the issue of mismatch base pair repair.
Earlier very little structural or quantitative data was available about polymerase error frequency (Goodman, et al., Journal of Molecular Biology, 88:423,1974), polymerase error correction, and mismatch base pair repair. These issues have been clarified significantly (Kramer, et al., Cell, 38:879, 1984). An important caution for the designer of complementary base pairs is that the relationship between the ultimate fidelity of reproduction of genetic information and the strength of interaction between different bases is not physically unique.